Human tryptophanyl-tRNA synthetase is an IFN-γ-inducible entry factor for Enterovirus

The Journal of Clinical Investigation
Man Lung YeungKwok-Yung Yuen

Abstract

Enterovirus A71 (EV-A71) receptors that have been identified to date cannot fully explain the pathogenesis of EV-A71, which is an important global cause of hand, foot, and mouth disease and life-threatening encephalitis. We identified an IFN-γ-inducible EV-A71 cellular entry factor, human tryptophanyl-tRNA synthetase (hWARS), using genome-wide RNAi library screening. The importance of hWARS in mediating virus entry and infectivity was confirmed by virus attachment, in vitro pulldown, antibody/antigen blocking, and CRISPR/Cas9-mediated deletion. Hyperexpression and plasma membrane translocation of hWARS were observed in IFN-γ-treated semipermissive (human neuronal NT2) and cDNA-transfected nonpermissive (mouse fibroblast L929) cells, resulting in their sensitization to EV-A71 infection. Our hWARS-transduced mouse infection model showed pathological changes similar to those seen in patients with severe EV-A71 infection. Expression of hWARS is also required for productive infection by other human enteroviruses, including the clinically important coxsackievirus A16 (CV-A16) and EV-D68. This is the first report to our knowledge on the discovery of an entry factor, hWARS, that can be induced by IFN-γ for EV-A71 infection. Given that ...Continue Reading

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Citations

Aug 2, 2019·Future Microbiology·Xingjian WenAnchun Cheng
Jan 12, 2020·Journal of Biomedical Science·Kyousuke Kobayashi, Satoshi Koike
Jun 20, 2019·Journal of Biomedical Science·Collins Oduor Owino, Justin Jang Hann Chu
Dec 4, 2019·Journal of Biomedical Science·Kuan-Ru Chen, Pin Ling
Mar 11, 2020·Frontiers in Microbiology·Bo-Shiun ChenShin-Ru Shih
Oct 16, 2018·The Journal of Clinical Investigation·Stanley Perlman, Tom Gallagher
Dec 5, 2019·Therapeutic Advances in Vaccines and Immunotherapy·Hui Xuan Lim, Chit Laa Poh
Jan 28, 2021·Viruses·Christine E Peters, Jan E Carette
Dec 11, 2020·Cell & Bioscience·Chuanjie ZhangJingfeng Li

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Datasets Mentioned

BETA
GSE80407

Methods Mentioned

BETA
PCR
flow cytometry
immunoprecipitation
pulldown
pull down
flow
confocal microscopy
FCS
chip
Assay

Software Mentioned

Ingenuity Pathway Analysis program (
Affymetrix GCOS
Affymetrix
PANGENIA
QIAGEN
FlowJo

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